Discovery in mouse brain may lead to new Parkinson's drugs
NEW YORK, Sep 01, 1999 (Reuters Health) -- Researchers have uncovered
the mechanism by which two chemicals in the brains of mice interact to
control movement, findings that could lead to the development of new
drugs to treat Parkinson's disease.
Parkinson's disease is a chronic nervous system disorder characterized
by a tremor that begins in the hand or food and then spreads, muscular
rigidity and slow speech.
``Our findings offer new perspectives for the treatment of Parkinson's
disease and other movement disorders that are characterized by an
imbalance between muscarinic cholinergic and dopaminergic
neurotransmission,'' concludes Jesus Gomeza and colleagues.
Acetylcholine and dopamine are two types of chemical messengers, or
neurotransmitters, that carry signals from brain cell to brain cell.
Each chemical interacts with a specific type of receptor -- cholinergic
or dopaminergic -- on the surfaces of the cells.
The researchers with the National Institute of Diabetes and Digestive
and Kidney Diseases and the pharmaceutical company Eli Lilly created
genetically altered mice that lacked a gene involved in the control of
movement and the ability to sense pain. The gene, which produces the M4
muscarinic acetylcholine receptor, is normally prominent throughout the
central nervous system.
The study findings, published in the Proceedings of the National Academy
of Science, explain how M4 receptors interact with dopaminergic
receptors to control movement. While scientists have known that
communication between these two receptors is skewed in people with
Parkinson's disease, they did not understand how the receptors interact.
Results indicate that the mice which lacked the M4 gene, and thus lacked
M4 receptors, were significantly more active than normal mice. When
given drugs that stimulated dopamine receptors, the experimental mice
were even more active.
Drugs that stimulate dopamine are generally used to treat Parkinson's
disease. The study suggests drugs that block M4 receptors may be more
beneficial, the researchers conclude.
``The development of centrally acting, selective M4 receptor antagonists
therefore remains an attractive therapeutic goal,'' the authors write.
SOURCE: Proceedings of the National Academy of Sciences
1999;96:10483-10488.
Copyright © 1996-1999 Reuters Limited.
--
Judith Richards, London, Ontario, Canada
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